Steroids substituted in the C.sub.11 position with an unsaturated substituent are known. U.S. Pat. No. 3,927,046 discloses 11-methylene and 11-(alkyl substituted)methylene steroids, U.S. Pat. No. 4,292,251 discloses 11.beta.-substituted unsaturated aliphatic hydrocarbon substituents containing 2-3 carbon atoms. Neither of these patents discloses any halogen substitution.
Difluoromethyl steroids are known with the difluoro substituent at C.sub.11, see U.S. patent application Ser. No. 639,285, filed Aug. 8, 1984 fee has been paid.
Steroids containing a fluoromethylene group (.dbd.CHF) are known. (E)-11-fluoromethylene and (Z)-11-fluoromethylene steroids are known, see U.S. patent application Ser. No. 639,285, filed Aug. 8, 1984 for fee has been paid.
Difluoromethylene steroids are known with the difluoromethylene substituent at C.sub.3 (U.S. Pat. No. 3,450,720), C.sub.6 (U.S. Pat. No. 3,504,002), C.sub.16 (U.S. Pat. No. 3,705,182) and C.sub.16 and C.sub.17 (U.S. Pat. No. 3,457,285). None of these references has the difluoromethylene substituent at C.sub.11 or even near it.
M. Obayashi et al. in Tetrahedron Letters 23, 2323 (1982) describe a process to prepare (diethylphosphinyl)difluoromethyllithium by reacting diethyl difluoromethylphosphonate and lithium diisopropylamide in THF at -78.degree.. The (diethylphosphinyl)difluoromethyllithium was reacted with ketones producing difluoromethylene compounds. None of the ketones used were steroids or even polycyclic or sterically-hindered as are the protected 11-keto steroids (III) of the present invention. The yields obtained by Obayashi were in the range of 54 to 75%; it is surprising and unexpected that the sterically-hindered (11-difluoromethylene steroids (IV) are obtained in yields of 70-80%.